1. Prof. Hanan Hagar Pharmacology Department College of Medicine
Antiemetics
Prof. Hanan Hagar
Pharmacology Department
College of Medicine

2. Learning objectives
Classify the main different classes of antiemetic drugs according to their mechanism of action.
Know the characteristic pharmacokinetics & dynamics of different classes of antiemetic drugs.
Identify the selective drugs that can be used according to the cause of vomiting.
Learn the Adjuvant antiemetics.
Describe the major side effects for the different classes of antiemetics.

3. Causes of Vomiting
Nausea and vomiting may be manifestations of many conditions and may occur due to stimulation of vomiting center that respond to inputs from:
Chemoreceptor trigger zone (CTZ) stimulation
Disturbance of vestibular system
Higher cortical centers stimulation (CNS)
The periphery (Pharynx, GIT) via sensory nerves

4. CTZ is physiologically outside BBB.
1. Chemoreceptor trigger zone stimulation
CTZ is an area of medulla that communicate with vomiting center to initiate vomiting.
CTZ is physiologically outside BBB.
CTZ Contains opioid receptors, D2 receptors & 5 HT3 receptors, Substance P
stimulated by:
Drugs (opioids, general anesthetics),
Chemicals and toxins in blood, CSF.
Radiation.

5. 2. The periphery via sensory nerves
GIT irritation, myocardial infarction, renal or
biliay stones.
3. Disturbance of vestibular system
by motion sickness
4. Higher cortical centers stimulation:
emotional factors, nauseating smells or sights.

6. Receptors Associated with Nausea and Vomiting

7. Pathophysiology of Emesis
Cerebral cortex
chemotherapy
Opioids
Anesthetics
Smell
Sight
Thought
Anticipatory emesis
ChemoreceptorTrigger Zone
(CTZ)
Vestibular nuclei
Vomiting Centre (medulla)
Motion sickness
Muscarinic Histaminic H1
Muscarinic, 5 HT3 & Histaminic H1
(Outside BBB)
5 HT3
Dopamine D2
Opioid receptors
Substance p
Chemo & radio therapy Gastroenteritis
Pharynx & GIT
5 HT3 receptors

8. Ach (Muscarinic receptors) Dopamine (D2)
Chemical transmitters & receptors involved in vomiting include:
Ach (Muscarinic receptors)
Dopamine (D2)
Histamine (Histaminergic receptors H1)
Serotonin (5 -HT3)
Substance P (Neurokinin receptors, NK1)
Opioid (Opioid receptors)

9. Classification of Antiemetic Drugs
5-HT3 antagonists
D2 receptor antagonists
NK1 antagonists
H1-receptor antagonists
Muscarinic receptor antagonists
Cannabinoids
Glucocorticoids

11. 5-HT3 antagonists Drugs as Ondansetron, Granisetron
Orally or parenterally
Potent antiemetic effects
Block 5-HT3 receptor in vomiting center, CTZ and 5HT3 receptors on intestinal vagal afferents.

12. Uses of 5-HT3 antagonists
First choice for prevention of:
Chemotherapy-induced nausea and vomiting (CINV) especially cisplatin.
Post-radiation NV& Post-operative NV
Their effects is increased by combination with corticosteroids and NK1 antagonists.
Side effects
Well tolerated
mild headache, dizziness and constipation
minor ECG abnormalities (QT prolongation)

13. D2 receptor antagonists
block D2 dopamine receptors in the CTZ
Two types exist:
Prokinetics drugs
Neuroleptics (antipsychotics)
Uses of D2 receptor antagonists
are among the most commonly used drug for nausea and vomiting of non-specific causes.
Effective against vomiting due to drugs,
gastroenteritis, post-operative, toxins, uremia, radiation.

14. D2 receptor antagonists 1) Prokinetics drugs
Drugs as metoclopramide, domperidone
Both are prokinetic agents due to their 5 HT4 agonistic activity.
used in GERD (gastroesophageal reflux disease), gastroparesis.
Used as antiemetics (blocking D2 receptors)
Metoclopramide crosses BBB but domperidone cannot (both have antiemetic effects as CTZ is outside BBB).

15. Side effects (only for metoclopramide):
Dyskinesia (extra-pyramidal side effects),
Galactorrhea, menstrual disorders, impotence.
Sedation, postural hypotension.

16. D2 receptor antagonists
Neuroleptics (Antipsychotics)
Chlorpromazine (CPZ), droperidol
used for postoperative vomiting and chemotherapy-induced nausea & vomiting.
Side effects: extrapyramidal symptoms sedation, postural hypotension

17. Neurokinin1 (NK1) receptor antagonists
Aprepitant
Is a substance P antagonists that acts by blocking neurokinin 1 receptors.
Orally
Used in prevention of acute and delayed chemotherapy-induced nausea and vomiting and for prevention of postoperative nausea and vomiting.
Usually combined with 5-HT3 antagonists and corticosteroids.

18. H1-receptor antagonists
Effective for motion sickness, morning sickness in pregnancy
Drugs as
Diphenhydramine
Meclizine - Cyclizine
Promethazine: severe morning sickness of pregnancy (if only essential).
Side effects:
prominent sedation, hypotension, anticholinergic effects (dry mouth, dilated pupils, urinary retention, constipation.

19. Muscarinic receptor antagonists
Hyoscine (scopolamine)
Orally, injection, patches
Used as transdermal patches in motion sickness (applied behind the external ear).
Not in chemotherapy-induced vomiting
Side effects: tachycardia, blurred vision, dry mouth, constipation, urinary retention (atropine-like actions).

20. Cannabinoids Nabilone, dronabinol mechanism of action not understood.
act at central cannabinoid receptors.
Used in vomiting due to cytotoxic anticancer drugs (adjuvant therapy).
Not commonly used.
Side effects: euphoria, dysphoria, sedation,
hallucination.

21. Glucocorticoids Dexamethasone - methylprednisolone
Used in chemotherapy-induced vomiting
combined with 5-HT3 antagonists or NK1 receptor antagonists.

22. Glucocorticoids Side effects: Hyperglycemia Hypertension Cataract
Osteoporosis
Increased intraocular pressure
Increased susceptibility to infection
Increased appetite & obesity

23. Summary
The choice of antiemetic depends on the etiology
Motion sickness
Muscarinic antagonists
Antihistaminics
Vomiting with pregnancy (morning sickness)
avoid all drugs in the first trimester
Pyridoxine (B6)
Promethazine ( late pregnancy).

24. Drug- induced vomiting (CTZ)
Dopamine antagonists
Post operative nausea & vomiting
5-HT3 antagonists
NK1 antagonists
Vomiting due to cytotoxic drugs.
D2- antagonists
Glucocorticoids
Cannabinoids

25. Thank you Questions ? 25